The Kansas City Chiefs are back on the field on Friday, when they face divisional rivals, the Los Angeles Chargers, to start the 2025 NFL season. The reigning AFC West champions come off a painful defeat against the Philadelphia Eagles in Super Bowl LIX, which prompted many to doubt them ahead of this campaign.

As long as they have Patrick Mahomes and Andy Reid, the Chiefs will have a shot against anybody. The season will start with a big test against the Chargers, one of the teams that got better in the offseason, to try to challenge Kansas City.

The Denver Broncos and Las Vegas Raiders also have intriguing projects coming into this season, but the Chargers appear to start the campaign as the Chiefs’ biggest obstacle in the division.

Sao Paulo will host an NFL game for a second consecutive season, this time a divisional game that could have ramifications down the stretch.

The Chiefs went 0-3 in the preseason, meaning Friday's game could be their first win since the dramatic victory over the Buffalo Bills in the 2024 AFC championship game. Jim Harbaugh’s team won’t be easy at all, but the Chiefs have the numbers in their favor (seven straight wins over the Chargers).

More than that, three keys in this game could secure a Chiefs’ win and start the campaign on the right foot.

Patrick Mahomes Delivers in Season Openers

Patrick Mahomes is a lock for Week 1 games. The two-time NFL MVP has played in seven season openers since becoming a full-time starter in 2018, going 162-of-234 for 2,056 yards and 21 touchdowns. If he continues playing at this high level to start this season, the Chargers will have a hard time trying to stop him.

Coincidentally, the Chargers were his opponents in the first season opener of his career. He connected on 15 of 27 pass attempts for 256 yards and four touchdowns. While Mahomes had his worst individual season in 2024, he is set to bounce back and help his team return to the Super Bowl.

In 12 games against the Chargers, Mahomes has gone 278-of-433, 3,270 yards passing and 27 touchdowns against seven interceptions. He has a passer rating of 101.1 against the Chargers. Los Angeles is one of Mahomes’ favorite victims, and if the trend continues, the Chiefs will add another win against the Chargers.

Justin Herbert Has One Reliable Wide Receiver

Justin Herbert entered the league as one of the most electrifying quarterback prospects in 2020. His deep throws and athleticism have earned him plenty of fans, but his doubters have enjoyed watching him fail when his team needs him the most. Herbert's new connection with second-year wide receiver Ladd McConkey could cause damage to the Chiefs' defense, but the lack of a solid WR2 could help the Chargers' plans.

Quentin Johnston is still dropping passes and Tre Harris didn't have the best showing during training camp. Keenan Allen's return could help Herbert, but outside of that, the Chiefs might not have much trouble shutting down the Chargers' aerial game.

The Chiefs’ Running Game Must Take Over Early

After a tumultuous 2024 season in which multiple wide receivers suffered injuries, with some even missing the entire season, the Chiefs enter the 2025 campaign with a different approach. The offense might rely on its running game more than anything, especially after Rashee Rice received a six-game suspension.

Xavier Worthy is still on the roster and ready to dominate, but outside of him, Marquis Brown and JuJu Smith-Schuster are two steps behind the second-year wideout.

Isaiah Pacheco, Kareem Hunt, Elijah Mitchell and Brashard Smith are in the running back room for this season. Pacheco and Hunt are more likely to get touches than anybody else, which could present big opportunities for Kansas City.

The Chiefs ran for 1,790 total rushing yards last season, while the Chargers' defense allowed 1,997. The Californians have a renewed defense, while the Chiefs' offensive line suffered changes in the offseason (they will start a new left guard and tackle this season), which could turn things around this time.

Still, Kansas City's running game helped them many times last season, and this one doesn't seem to be any different.